2022-RA-653-ESGO the Impact of Histology, Prior Therapy, and Dmmr Status on Lenvatinib + Pembrolizumab Outcomes in Patients with Advanced Endometrial Cancer: A Subgroup Analysis of Study 309/KEYNOTE-775

Introduction/Background In the phase 3 Study 309/KEYNOTE-775 (Makker 2022, NEJM), lenvatinib plus pembrolizumab (L+P) demonstrated statistically and clinically significant improvements in progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician’s choice (TPC) in previously treated advanced endometrial cancer (aEC; in mismatch-repair proficient [pMMR] and all-comer patients). In this updated analysis (data cutoff: March 1, 2022), we report efficacy by histology, prior therapy, and deficient (d)MMR status. Methodology Pts with aEC and 1 prior platinum-based chemotherapy regimen (up to 2 if 1 was given in the neoadjuvant/adjuvant setting) were randomized (1:1) to L 20 mg orally once daily + P 200 mg IV every 3 weeks (Q3W) or TPC (doxorubicin at 60 mg/m2 IV Q3W or paclitaxel at 80 mg/m2 IV QW [3 weeks on; 1 week off]). Randomization was stratified by MMR status; pMMR patients were further stratified by Eastern Cooperative Oncology Group Performance Status, geographic region, and history of pelvic irradiation. We report PFS, OS, and ORR (by blinded independent central review per RECIST v1.1) by histology (endometrioid vs non-endometrioid), prior therapy (1, 2, ≥3 lines), and dMMR status. Results 827 patients were randomized to L+P (n=411) or TPC (n=416). PFS and OS in all-comers favored L+P regardless of histology (PFS HR, endometrioid: 0.54/non-endometrioid: 0.55; OS HR, endometrioid: 0.63/non-endometrioid: 0.61), prior therapy (PFS HR: 1 line, 0.49/2 lines, 0.68/≥3 lines, 0.61; OS HR: 1 line, 0.63/2 lines, 0.64/≥3 lines, 0.69), or dMMR status (PFS HR, 0.39; OS HR, 0.43) (table 1). The table 1 also shows PFS, OS, and ORR in all-comers and pMMR patients. Conclusion PFS, OS, and ORR continued to favor L+P vs TPC in all subgroups of interest, including patients with dMMR tumors. These data further support L+P as a standard therapy in previously treated aEC.